Diagnostic Criteria

Formal diagnostic criteria for Huppke-Brendel syndrome (HBS) have not been established.

Suggestive Findings

HBS should be suspected in individuals with the following clinical, radiographic, electrophysiologic, and laboratory findings.

Clinical findings

• Bilateral congenital cataracts

• Nystagmus

• Sensorineural hearing loss

• Severe developmental delay/ intellectual disability and regression of acquired milestones

• Hypotonia

• Seizures

• Poor weight gain and growth deficiency

Radiographic findings (on brain MRI examination)

• Cerebellar hypoplasia/ cerebellar atrophy

• Cerebral atrophy

• Hypomyelination/dysmyelination

• White matter volume loss

• Wide subarachnoid spaces

• Posterior cranial fossa cyst

Electrophysiologic findings. Brain stem auditory evoked potentials show absent wave forms.

Laboratory findings

Source: GeneReviews — "Huppke-Brendel Syndrome"

Differential Diagnosis

Disorders with low copper and ceruloplasmin in the differential diagnosis of Huppke-Brendel Syndrome are listed in . Table 2. Differential Diagnosis of Huppke-Brendel Syndrome: Disorders of Copper Metabolism

Management Guidelines

No clinical practice guidelines for Huppke-Brendel syndrome (HBS) have been published. In the absence of published guidelines, the following recommendations are based on the authors' personal experience managing individuals with this disorder.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with HBS, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

Huppke-Brendel Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Eyes | Ophthalmology eval | To assess for cataracts, reduced vision, abnormal ocular movement, best corrected visual acuity, refractive errors, strabismus

Hearing

| Audiology eval | Incl brain stem auditory evoked response otoacoustic emissions testing

Neurologic

| • Complete neurologic assessment

• EEG if seizures are suspected

|

Gastrointestinal/

Feeding

| Gastroenterology/ nutrition/ feeding team eval | • To incl eval of aspiration risk nutritional status

• Consider eval for gastrostomy tube placement in persons w/dysphagia /or aspiration risk.

Development

| Developmental assessment | • To incl motor, adaptive, cognitive, speech-language eval

• Eval for early intervention/ special education

Musculoskeletal

| Orthopedics/ physical medicine rehab/ PT OT eval | To incl assessment of:

Source: GeneReviews — "Huppke-Brendel Syndrome"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended.

Table 5.

Huppke-Brendel Syndrome: Recommended Surveillance

System/Concern | Evaluation | Frequency

Ophthalmologic involvement

| Ophthalmology eval | Per treating ophthalmologist(s)

Hearing

| Audiology eval | Annually or per audiologist

Feeding

| • Measure growth parameters.

• Evaluate nutritional status safety of oral intake.

| At each visit

Development

| Monitor developmental progress educational needs.

Neurologic

| Assess for new seizures/ monitor those w/seizures as clinically indicated.

Musculoskeletal

| • Physical medicine, OT/PT assessment of mobility, self-help skills

• Assess for scoliosis contractures.

Family/Community

| Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources), care coordination, or follow-up genetic counseling if new questions arise (e.g., family planning).

OT = occupational therapy; PT = physical therapy

Source: GeneReviews — "Huppke-Brendel Syndrome"